Many poorly water soluble therapeutic compounds exist in a physical state that is highly crystalline. Additionally such high crystalline therapeutic compounds often have high melting points. By converting the physical state of such a therapeutic compound into an amorphous state allows for both greater solubility and faster dissolution of the therapeutic compound. This, thus, may increase the bioavailability of the drug.
Various methods have been used to achieve an amorphous state that results in the therapeutic compound being molecularly dispersed in an inert carrier, typically a polymer. Such methods include solvent evaporation, spray drying, and melt fusion. Not all of these processes are ideal for converting the highly crystalline therapeutic compound into an amorphous state. Some methods may result in a product that reverts back, or recrystallizes, into a crystalline state. Other methods utilize organic solvents which may not be desirable due to environmental and safety reasons.
Of particular interest is melt extrusion which uses a twin screw extruder to combine a therapeutic compound with an inert carrier to form a solid dispersion. Typically, the twin screw extruder is heated to facilitate mixing of the therapeutic compound with the carrier. Sometimes heating a melt extruder to a temperature above the melting point of a therapeutic compound may not be suitable since that temperature could exceed the melting point of the carrier, thus causing the carrier to decompose. Additionally, some therapeutic compounds may decompose when melted.
Thus, there is a need for a process that allows for the use of melt extrusion to convert the physical state of a therapeutic compound from being highly crystalline to amorphous that is particularly appropriate for therapeutic compounds that have either a high melting point and/or an attribute of decomposing near or at its melting point. This invention addresses such a need by utilizing a melt extrusion process that incorporates a solubilizing agent. This solubilizing agent allows the processing temperature for a therapeutic compound to be lowered in order to preserve the integrity of the therapeutic compound while allowing for the physical state of the therapeutic compound to change from crystalline to amorphous. Furthermore, having such a process expands the formulation possibilities, as carriers or polymers that would normally decompose at high temperatures may be subsequently used providing greater flexibility for the pharmaceutical formulator.